Autoimmunity and Autoimmune Disease Romana Siddique BTE 303

Autoimmunity Origins Horror autotoxicus: Literally, the horror of self-toxicity. A term coined by the German immunologist Paul Ehrlich (1854-1915) to describe the body's innate aversion to immunological self-destruction.

What is autoimmunity and Autoimmune disease? Autoimmunity: production of auto antibodies and autoreactive T cells. Autoimmune disease: those cases where autoimmune process contributes to the pathogenesis of the disease rather than situations, where apparently harmless auto antibodies are formed following tissue damage. Example of autoimmune disease: Hashimoto’s thyroiditis

Types of autoimmune diseases Autoimmune diseases are of two types: 1. Organ specific: are those where antibodies and invasive destructive lesions are directed against one organ of the body Target organs are- Thyroid, adrenals, stomach and pancreas Example-Hasimoto’s Thyroiditis, Thyrotoxicosis, Myasthania Gravis 2. Nonorgan specific or Systemic: are those where antibodies and lesions are directed to antigens which are widespread throughout the body. Example: Rheumatological disorders characteristically involve the skin, kidney, joints and muscle

Two types of Autoimmune disease

Incidence of autoimmune diseases Genetic Factors: Families: Autoimmune disease can occur in families. This is largely genetic rather than environmental. HLA: Certain HLA haplotypes predispose to autoimmunity. Sex: Females have a far higher incidence of autoimmunity than males, perhaps due to hormonal influences. Environmental Factors: Microbes: Infection can diffuse autoimmune disease e.g; group A Streptococcus is associated with Rheumatoid fever because antibodies against this organism have homology with heart muscle and can affect the heart . Nonmicrobial factors: Fish oil or cod liver oil are beneficial for patient with rheumatoid arthritis

Some Autoimmune diseases in humans

Myasthania Gravis Organ specific autoimmune disease mediated by blocking antibodies. A patient with this disease produces auto-antibodies that bind the acetylcholine receptors on the motor end-plates of muscles, blocking the normal binding of acetylcholine and also inducing complement mediated lysis of the cells. The result is a progressive weakening of the skeletal muscles Ultimately, the antibodies destroy the cells bearing the receptors. Symptoms: early signs include drooping eyelids and inability to retract the corners of the mouth, which gives the appearance of snarling. Progressive weakening of the muscle leads to severe impairment of eating as well as problems with movement.

How blocking auto-Abs works in Myasthania Greavis

Graves’ Disease Mediated by stimulating auto-Abs. The production of thyroid hormones is carefully regulated by thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. Binding of TSH to a receptor on thyroid cells activates adenylate cyclase and stimulates the synthesis of two thyroid hormones, thyroxine and triiodothyronine. A patient with Graves’ disease produces auto-antibodies that bind the receptor for TSH and mimic the normal action of TSH, activating adenylate cyclase and resulting in production of the thyroid hormones. Unlike TSH, the autoantibodies are not regulated, and consequently they overstimulate the thyroid. For this reason these auto-antibodies are called long-acting thyroid-stimulating (LATS) antibodies.

Symptoms of Graves’ disease Goiter Increased sweating Rapid Heart-beat Thinning of hair Brittle Hair Redding and thickening of skin Weight loss Heat Insensitivity

How stimulating Auto-Abs work in Graves’ Disease?

Systemic Lupus Erythematosus (SLE) One of the best examples of a systemic autoimmune disease typically appears in women between 20 and 40 years of age; the ratio of female to male patients is 10:1. Affected individuals may produce autoantibodies to a vast array of tissue antigens, such as DNA, histones, RBCs, platelets, leukocytes, and clotting factors. Interaction of these auto-antibodies with their specific antigens produces various symptoms. SLE is characterized by fever, weakness, arthritis, skin rashes and kidney dysfunction.

Systemic Lupus Erythematosus (SLE) contd. Auto-antibody specific for RBCs and platelets,can lead to complement-mediated lysis, resulting in hemolytic anemia and thrombocytopenia, respectively. When immune complexes of auto-antibodies with various nuclear antigens are deposited along the walls of small blood vessels, a type III hypersensitive reaction develops. The complexes activate the complement system and generate membrane-attack complexes and complement split products that damage the wall of the blood vessel, resulting in vasculitis and glomerulonephritis

Systemic Lupus Erythematosus (SLE) contd. Excessive complement activation in patients with severe SLE produces elevated serum levels of the complement split products C3a and C5a, which may be three to four times higher than normal. C5a induces increased expression of the type 3 complement receptor (CR3) on neutrophils, facilitating neutrophil aggregation and attachment to the vascular endothelium. As neutrophils attach to small blood vessels, the number of circulating neutrophils declines (neutropenia) and various occlusions of the small blood vessels develop (vasculitis). These occlusions can lead to widespread tissue damage.